3,4,5,6-Tetrahydrophthalic anhydride → 2,3,5,6,7,8-Hexahydrophthalazine-1,4-dione

HRID 2197412Notes

Reaction equation

HRID 2197412 reaction equation
[C:1]1(=O)[O:6][C:4](=[O:5])[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][C:2]1=2.O.[NH2:13][NH2:14].C([O-])(=O)C.[Na+]>C(O)(=O)C>[C:4]1(=[O:5])[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][C:2]=2[C:1](=[O:6])[NH:14][NH:13]1

Participants

5

Reactant 3

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 24654Hydrazine hydrate (1:1)HCID 517045Sodium Acetate

Product 1

HCID 3139202,3,5,6,7,8-Hexahydrophthalazine-1,4-dione

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,4,5,6-tetrahydrophthalic anhydride (3.5 g, 23 mmol), hydrazine hydrate (2.0 mL), sodium acetate (15.4 g, 188 mmol) in 100 mL of acetic acid is heated at 100° C. overnight. Upon cooling, a white solid is formed and collected by filtration. The solid is washed with water and dried to give 2,3,5,6,7,8-hexahydro-phthalazine-1,4-dione. The solid is taken up in 15 mL of POCl3. The resultant mixture is heated at reflux overnight. After cooled, the excess POCl3 is removed under reduced pressure. Crushed ice is added to the residue followed by careful addition of solid Na2CO3 to pH 9. The product is extracted with EtOAc twice. The combined extract is washed with brine, dried and concentrated. The residue is purified by flash silica gel column (Hexanes/EtOAc 4:1) to give 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine as a white solid. 1H NMR: (CDCl3) 2.74 (m, 4H), 1.87 (m, 4H).

Workup

  1. temperatureUpon cooling
  2. customa white solid is formed
  3. filtrationcollected by filtration
  4. washThe solid is washed with water
  5. customdried

Sources & evidence

ORD record
ord-afdcdabcbbe848de93cfb50fa293e269
Source dataset
uspto-grants-2012_12
Patent number
US08338591B2

Reaction notes

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